The group's initial line up, which remained unchanged until about issue 72, consisted of rocket scientist Reed Richards ("Mr. Fantastic"), test pilot Ben Grimm ("The Thing"), Reed's girlfriend Sue Storm ("Invisible Girl"), and her kid brother Johnny ("The Human Torch"). Very few biographical details were supplied in the first issue, but the characters were fleshed out within the next five months.

Writer/editor Stan Lee originally proposed the Fantastic Four as Marvel's answer to DC's Justice League of America, collaborating with veteran cartoonist Jack Kirby to rough out the first two stories. The concept was seen as something of a departure from the traditional super hero formula: the Four had no secret identities and (initially) no costumes; they squabbled and bickered like school kids; and to top it off, the Thing was just plain ugly.

Much of the original concept can be traced back to earlier Jack Kirby strips employing a similar premise (Challengers of the Unknown, DC) and to the 'giant monster' themes being exploited in Marvel's sci-fi titles (Tales to Astonish, Amazing Adult Fantasy, etc). The first issue was, in fact, little different to any one of a dozen alien menace stories Kirby had drawn over the last four years. However, the book's artwork and storylines would become increasingly more sophisticated as Lee and Kirby steered the series towards 'Universal' concepts (such as the world-devouring Galactus), technologically advanced civilizations (The Inhumans), and complex social social issues (racial prejudice, alienation, the threat of nuclear destruction).

Lee and Kirby would hit their stride in issue five, with the introduction of Dr. Doom, Marvel's archetypal villain and personification of intellectual darkness. From there, the comic would evolve from a run-of-the-mill space opera to the foundation of the so-called "Marvel Universe."